With the use of numerous preparations, including a cell-free system from rat brain, rat pineal gland in organ culture, and the adrenergic neuroblastoma N1E115, we are investigating the tetrahydrobiopterin (BH4) biosynthetic pathway and the cellular processes which regulate this synthesis. We have also begun preliminary investigations, with the use of a regenerating rat liver preparation and the developing rat brain and pineal gland, into the possible role of BH4 in cellular proliferation.